Neonatal reference intervals for thyroid stimulating hormone and free thyroxine assayed on a Siemens Atellica® IM analyzer: a cross sectional study.

BACKGROUND: Deriving population specific reference intervals (RIs) or at the very least verifying any RI before adoption is good laboratory practice. Siemens has provided RIs for thyroid stimulating hormone (TSH) and free thyroxine (FT4) determined on their Atellica® IM analyzer for all age groups except the neonatal age group which provides a challenge for laboratories that intend to use it to screen for congenital hypothyroidism (CH) and other thyroid disorders in neonates. We set out to determine RIs for TSH and FT4 using data obtained from neonates undergoing routine screening for CH at the Aga Khan University Hospital, Nairobi, Kenya. METHODOLOGY: TSH and FT4 data for neonates aged 30 days and below were extracted from the hospital management information system for the period March 2020 to June 2021. A single episode of testing for the same neonate was included provided both TSH and FT4 were done on the same sample. RI determination was performed using a non-parametric approach. RESULTS: A total of 1243 testing episodes from 1218 neonates had both TSH and FT4 results. A single set of test results from each neonate was used to derive RIs. Both TSH and FT4 declined with increase in age with a more marked decline seen in the first 7 days of life. There was a positive correlation between logFT4 and logTSH (rs (1216) = 0.189, p = < 0.001). We derived TSH RIs for the age groups 2-4 days (0.403-7.942 µIU/mL) and 5-7 days (0.418-6.319 µIU/mL), and sex specific RIs for males (0.609-7.557 µIU/mL) and females (0.420-6.189 µIU/mL) aged 8-30 days. For FT4, separate RIs were derived for the age groups 2-4 days (1.19-2.59 ng/dL), 5-7 days (1.21-2.29 ng/dL) and 8-30 days (1.02-2.01 ng/dL). CONCLUSION: Our neonatal RIs for TSH and FT4 are different from those published or recommended by Siemens. The RIs will serve as a guide for the interpretation of thyroid function tests in neonates from sub-Saharan Africa where routine screening for congenital hypothyroidism using serum samples is done on the Siemens Atellica® IM analyzer.

Is HbA1c associated with birth weight? A multivariable analysis of Pakistani pregnant women.

AIM: Globally, one in seven infants is born with low birth weight and 3%-7% of infants are born with high birth weight, with the greatest burden noted in low- and middle-income countries. This study investigated the association between maternal prenatal glucose regulation and birth weight and the moderating effect of fetal sex among Pakistani women. METHODS: Secondary data from a prospective longitudinal study of healthy pregnant women from Pakistan (N = 189) was used. Participants provided a blood sample (12-19 weeks' gestational age) for the assessment of HbA1c (%). Birth weight (g) was collected following delivery. RESULTS: Higher maternal HbA1c was associated with higher birth weight (b = 181.81, t[189] = 2.15, p = 0.03), which was moderated by fetal sex (b = -326.27, t[189] = -2.47, p = 0.02), after adjusting for gestational age at birth, ethnicity, and pregnancy weight. Among women carrying a male fetus, every 1% increase in HbA1c predicted a 182 g increase in birth weight (b = 181.81, t[189] = 2.15, p = 0.03). CONCLUSIONS: Results extend research from high-income countries and indicate that fetal sex may have implications for glucose regulation in early to mid-pregnancy. Future research should examine sociocultural factors, which could elucidate potential mediating factors in the relation between HbA1c and birth weight in healthy pregnancies.

PRECISE pregnancy cohort: challenges and strategies in setting up a biorepository in sub-Saharan Africa.

BACKGROUND AND OBJECTIVE: PRECISE is a population-based, prospective pregnancy cohort study designed for deep phenotyping of pregnancies in women with placenta-related disorders, and in healthy controls. The PRECISE Network is recruiting ~ 10,000 pregnant women in three countries (The Gambia, Kenya, and Mozambique) representing sub-Saharan Africa. The principal aim is to improve our understanding of pre-eclampsia, fetal growth restriction and stillbirth. This involves the creation of a highly curated biorepository for state of the art discovery science and a rich database of antenatal variables and maternal and neonatal outcomes. Our overarching aim is to provide large sample numbers with adequate power to address key scientific questions. Here we describe our experience of establishing a biorepository in the PRECISE Network and review the issues and challenges surrounding set-up, management and scientific use. METHODS: The feasibility of collecting and processing each sample type was assessed in each setting and plans made for establishing the necessary infrastructure. Quality control (QC) protocols were established to ensure that biological samples are 'fit-for-purpose'. The management structures required for standardised sample collection and processing were developed. This included the need for transport of samples between participating countries and to external academic/commercial institutions. RESULTS: Numerous practical challenges were encountered in setting up the infrastructure including facilities, staffing, training, cultural barriers, procurement, shipping and sample storage. Whilst delaying the project, these were overcome by establishing good communication with the sites, training workshops and constant engagement with the necessary commercial suppliers. A Project Executive Committee and Biology Working Group together defined the biospecimens required to answer the research questions paying particular attention to harmonisation of protocols with other cohorts so as to enable cross-biorepository collaboration. Governance structures implemented include a Data and Sample Committee to ensure biospecimens and data will be used according to consent, and prioritisation by scientific excellence. A coordinated sample and data transfer agreement will prevent delay in sample sharing. DISCUSSION: With adequate training and infrastructure, it is possible to establish high quality sample collections to facilitate research programmes such as the PRECISE Network in sub-Saharan Africa. These preparations are pre-requisites for effective execution of a biomarker-based approach to better understand the complexities of placental disease in these settings, and others.

Vitamin D status in healthy black African adults at a tertiary hospital in Nairobi, Kenya: a cross sectional study.

BACKGROUND: Vitamin D has been known since the twentieth Century for its benefits in bone health. Recent observational studies have demonstrated its benefits in infectious diseases such as tuberculosis and non-communicable diseases such as diabetes mellitus, cardiovascular diseases and cancer. This has led to a dramatic increase in testing among adults. The cut-offs for vitamin D deficiency have been debated for decades and the current cut off is derived from a Caucasian population. Studies done among black African adults in Africa are few with vitamin D deficiency ranging from 5 to 91%. A few cut- offs have correlated vitamin D deficiency to physiological markers such as parathyroid hormone (PTH), calcium and phosphate with varying results. METHODS: This was a cross sectional study carried out among blood donors at Aga Khan University hospital, Nairobi (AKUHN) from March to May 2015. Vitamin D (25(OH)D) levels were assayed and correlated with PTH, calcium and phosphate. RESULTS: A total of 253 individuals were included in the final analysis. The proportion of study participants who had a 25(OH) D level of < 20 ng/ml thus classified as vitamin D deficient was 17.4% (95% C.I 12.73-22.07). The 25(OH) D level that coincided with a significant increase in PTH was 30 ng/ml. Males were less likely to be vitamin D deficient (O.R 0.48 (C.I 0.233-0.993) p 0.04). Sunshine exposure for ≥3 h per day reduced the odds of being Vitamin D deficient though this was not statistically significant after multivariate regression analysis. CONCLUSIONS: We found a much lower prevalence of Vitamin D deficiency compared to many similar studies carried out in sub-Saharan Africa possibly due to the recruitment of healthy individuals and the proximity of Nairobi to the equator which allows for considerable exposure to sunshine. Vitamin D levels below 30 ng/mL was associated with a significant rise in PTH levels, suggesting that this cut off could be appropriate for defining Vitamin D deficiency in the population served by our laboratory.

Metabolic syndrome and its predictors in an urban population in Kenya: A cross sectional study.

BACKGROUND: The metabolic syndrome (MetS) is a clustering of interrelated risk factors which doubles the risk of cardio-vascular disease (CVD) in 5-10 years and increases the risk of type 2 diabetes 5 fold. The identification of modifiable CVD risk factors and predictors of MetS in an otherwise healthy population is necessary in order to identify individuals who may benefit from early interventions. We sought to determine the prevalence of MetS as defined by the harmonized criteria and its predictors in subjectively healthy black Africans from various urban centres in Kenya. METHOD: We used data collected from healthy black Africans in Kenya as part of a global study on establishing reference intervals for common laboratory tests. We determined the prevalence of MetS and its components using the 2009 harmonized criterion. Receiver operator characteristic (ROC) curve analysis was used to determine the area under the curves (AUC) for various predictors of MetS. Youden index was used to determine optimum cut-offs for quantitative measurements such as waist circumference (WC). RESULTS: A total of 528 participants were included in the analysis. The prevalence of MetS was 25.6% (95% CI: 22.0%-29.5%). Among the surrogate markers of visceral adiposity, lipid accumulation product was the best predictor of MetS with an AUC of 0.880 while triglyceride was the best predictor among the lipid parameters with an AUC of 0.816 for all participants. The optimal WC cut-off for diagnosing MetS was 94 cm and 86 cm respectively for males and females. CONCLUSIONS: The prevalence of MetS was high for a healthy population highlighting the fact that one can be physically healthy but have metabolic derangements indicative of an increased CVD risk. This is likely to result in an increase in the cases of CVD and type 2 diabetes in Kenya if interventions are not put in place to reverse this trend. We have also demonstrated the inappropriateness of the WC cut-off of 80 cm for black African women in Kenya when defining MetS and recommend adoption of 86 cm.

Comparison of equations for estimating glomerular filtration rate in screening for chronic kidney disease in asymptomatic black Africans: a cross sectional study.

BACKGROUND: Several equations have been developed to estimate glomerular filtration rate (eGFR). The common equations used were derived from populations predominantly comprised of Caucasians with chronic kidney disease (CKD). Some of the equations provide a correction factor for African-Americans due to their relatively increased muscle mass and this has been extrapolated to black Africans. Studies carried out in Africa in patients with CKD suggest that using this correction factor for the black African race may not be appropriate. However, these studies were not carried out in healthy individuals and as such the extrapolation of the findings to an asymptomatic black African population is questionable. We sought to compare the proportion of asymptomatic black Africans reported as having reduced eGFR using various eGFR equations. We further compared the association between known risk factors for CKD with eGFR determined using the different equations. METHODS: We used participant and laboratory data collected as part of a global reference interval study conducted by the Committee of Reference Intervals and Decision Limits (C-RIDL) under the International Federation of Clinical Chemistry (IFCC). Serum creatinine values were used to calculate eGFR using the Cockcroft-Gault (CG), re-expressed 4 variable modified diet in renal disease (4v-MDRD), full age spectrum (FAS) and chronic kidney disease epidemiology collaboration equations (CKD-EPI). CKD classification based on eGFR was determined for every participant. RESULTS: A total of 533 participants were included comprising 273 (51.2%) females. The 4v-MDRD equation without correction for race classified the least number of participants (61.7%) as having an eGFR equivalent to CKD stage G1 compared to 93.6% for CKD-EPI with correction for race. Only age had a statistically significant linear association with eGFR across all equations after performing multiple regression analysis. The multiple correlation coefficients for CKD risk factors were higher for CKD-EPI determined eGFRs. CONCLUSIONS: This study found that eGFR determined using CKD-EPI equations better correlated with a prediction model that included risk factors for CKD and classified fewer asymptomatic black Africans as having a reduced eGFR compared to 4v-MDRD, FAS and CG corrected for body surface area.

Reference intervals for thyroid stimulating hormone and free thyroxine derived from neonates undergoing routine screening for congenital hypothyroidism at a university teaching hospital in Nairobi, Kenya: a cross sectional study.

BACKGROUND: In order to accurately interpret neonatal thyroid function tests (TFTs), it is necessary to have population specific reference intervals (RIs) as there is significant variation across different populations possibly due to genetic, environmental or analytical issues. Despite the importance of RIs, globally there are very few publications on RIs for neonatal TFTs primarily due to ethical and technical issues surrounding recruitment of neonates for a prospective study. To the best of our knowledge, this is the first report from Africa on neonatal RIs for TFTs. METHODS: We used hospital based data largely derived from neonates attending the wellness clinic at the Aga Khan University Hospital Nairobi (AKUHN) where screening for congenital hypothyroidism is routinely done. Specifically we derived age and gender stratified RIs for free thyroxine (fT4) and thyroid stimulating hormone (TSH) which had been analyzed on a Roche e601 analyzer from 2011 to 2013. Determination of reference intervals was done using a non-parametric method. RESULTS: A total of 1639 and 1329 non duplicate TSH and fT4 values respectively were used to derive RIs. There was a decline in TSH and fT4 levels with increase in age. Compared to the Roche RIs, the derived RIs for TSH in neonates aged 0-6 days and those aged 7-30 days had lower upper limits and narrower RIs. The fT4 lower limits for neonates less than 7 days and those aged 7-30 days were higher than those proposed by Roche. There was a significant difference in TSH RIs between male and female neonates aged less than 15 days. No gender differences were seen for all other age stratifications for both TSH and fT4. Appropriate age and gender specific RIs were subsequently determined. CONCLUSION: The AKUHN derived RIs for fT4 and TSH revealed similar age related trends to what has been published. However, the differences seen in upper and lower limits across different age stratifications when compared to the Roche RIs highlight the need for population specific RIs for TFTs especially when setting up a screening programme for congenital hypothyroidism. We subsequently recommend the adoption of the derived RIs by the AKUHN laboratory and hope that the RIs obtained can serve as a reference for the African population.

Comparison of Clinical Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing guidelines for the interpretation of antibiotic susceptibility at a University teaching hospital in Nairobi, Kenya: a cross-sectional study.

BACKGROUND: The Clinical Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines are the most popular breakpoint guidelines used in antimicrobial susceptibility testing worldwide. The EUCAST guidelines are freely available to users while CLSI is available for non-members as a package of three documents for US $500 annually. This is prohibitive for clinical microbiology laboratories in resource poor settings. We set out to compare antibiotic susceptibility determined by the two guidelines to determine whether adoption of EUCAST guidelines would significantly affect our susceptibility patterns. METHODS: We reviewed minimum inhibitory concentrations (MIC) of various antibiotics routinely reported for Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) isolates from an automated microbiology identification system (VITEK-2) at the Aga Khan University Hospital Nairobi's Pathology department. These MICs were then analyzed using both CLSI 2015 and EUCAST 2015 guidelines and classified as resistant, intermediate or susceptible. We compared the susceptibility and agreement between the CLSI and EUCAST categorizations. RESULTS: Susceptibility data from a total of 5165 E. coli, 1103 S. aureus and 532 P. aeruginosa isolates were included. The concordance rates of the two guidelines for E. coli, S. aureus and P. aeruginosa ranged from 78.2 to 100 %, 94.6 to 100 % and 89.1 to 95.5 % respectively. The kappa statistics for E. coli MICs revealed perfect agreement between CLSI and EUCAST for cefotaxime, ceftriaxone and trimethoprim-sulfamethoxazole, almost perfect agreement for ampicillin, ciprofloxacin, cefuroxime, gentamicin and ceftazidime, substantial agreement for meropenem, moderate agreement for cefepime and amoxicillin-clavulanate, fair agreement for nitrofurantoin and poor agreement for amikacin. For S. aureus the kappa statistics revealed perfect agreement for penicillin, trimethoprim-sulfamethoxazole, levofloxacin, oxacillin, linezolid and vancomycin, almost perfect agreement for clindamycin, erythromycin and tetracycline and moderate agreement for gentamicin. For P. aeruginosa the kappa analysis revealed moderate to almost perfect agreement for all the anti-pseudomonal antibiotics. CONCLUSION: The results show comparable antibiotic susceptibility patterns between CLSI and EUCAST breakpoints. Given that EUCAST guidelines are freely available, it makes it easier for laboratories in resource poor settings to have an updated and readily available reference for interpreting antibiotic susceptibilities.

Molecular characterization of Staphylococcus aureus isolates from various healthcare institutions in Nairobi, Kenya: a cross sectional study.

BACKGROUND: Staphylococcus aureus (S. aureus) has established itself over the years as a major cause of morbidity and mortality both within the community and in healthcare settings. Methicillin resistant S. aureus (MRSA) in particular has been a major cause of nosocomial infections resulting in significant increase in healthcare costs. In Africa, the MRSA prevalence has been shown to vary across different countries. In order to better understand the epidemiology of MRSA in a setting, it is important to define its population structure using molecular tools as different clones have been found to predominate in certain geographical locations. METHODS: We carried out PFGE, MLST, SCCmec and spa typing of selected S. aureus isolates from a private and public referral hospital in Nairobi, Kenya. RESULTS: A total of 93 S. aureus isolates were grouped into 19 PFGE clonal complexes (A-S) and 12 singletons. From these, 55 (32 MRSA and 23 MSSA) representative isolates from each PFGE clonal complex and all singletons were spa typed. There were 18 different MRSA spa types and 22 MSSA spa types. The predominant MRSA spa type was t037 comprising 40.6 % (13/32) of all MRSA. In contrast, the MSSA were quite heterogeneous, only 2 out of 23 MSSA shared the same spa type. Two new MRSA spa types (t13149 and t13150) and 3 new MSSA spa types (t13182, t13193 and t13194) were identified. The predominant clonal complex was CC 5 which included multi-locus sequence types 1, 8 and 241. CONCLUSION: In contrast to previous studies published from Kenya, there's marked genetic diversity amongst clinical MRSA isolates in Nairobi including the presence of well-known epidemic MRSA clones. Given that these clones are resident within our referral hospitals, adherence to strict infection control measures needs to be ensured to reduce morbidity and mortality associated with hospital acquired MRSA infections.

Ceftriaxone-resistant Salmonella enterica serotype typhimurium sequence type 313 from Kenyan patients is associated with the blaCTX-M-15 gene on a novel IncHI2 plasmid.

Multidrug-resistant bacteria pose a major challenge to the clinical management of infections in resource-poor settings. Although nontyphoidal Salmonella (NTS) bacteria cause predominantly enteric self-limiting illness in developed countries, NTS is responsible for a huge burden of life-threatening bloodstream infections in sub-Saharan Africa. Here, we characterized nine S. Typhimurium isolates from an outbreak involving patients who initially failed to respond to ceftriaxone treatment at a referral hospital in Kenya. These Salmonella enterica serotype Typhimurium isolates were resistant to ampicillin, chloramphenicol, cefuroxime, ceftriaxone, aztreonam, cefepime, sulfamethoxazole-trimethoprim, and cefpodoxime. Resistance to ß-lactams, including to ceftriaxone, was associated with carriage of a combination of blaCTX-M-15, blaOXA-1, and blaTEM-1 genes. The genes encoding resistance to heavy-metal ions were borne on the novel IncHI2 plasmid pKST313, which also carried a pair of class 1 integrons. All nine isolates formed a single clade within S. Typhimurium ST313, the major clone of an ongoing invasive NTS epidemic in the region. This emerging ceftriaxone-resistant clone may pose a major challenge in the management of invasive NTS in sub-Saharan Africa.

Low prevalence of methicillin resistant Staphylococcus aureus as determined by an automated identification system in two private hospitals in Nairobi, Kenya: a cross sectional study.

BACKGROUND: Staphylococcus aureus (S.aureus) is a major cause of both healthcare and community acquired infections. In developing countries, manual phenotypic tests are the mainstay for the identification of staphylococci with the tube and slide coagulase tests being relied upon as confirmatory tests for S. aureus. The subjectivity associated with interpretation of these tests may result in misidentification of coagulase negative staphylococci as S.aureus. Given that antibiotic resistance is more prevalent in CONS, this may result in over estimation of methicillin resistant S.aureus (MRSA) prevalence. METHODS: A review of susceptibility data from all non-duplicate S.aureus isolates generated between March 2011 and May 2013 by the Vitek-2 (bioMérieux) automated system was performed by the authors. The data was generated routinely from processed clinical specimens submitted to the microbiology laboratories for culture and sensitivity at the Aga Khan University Hospital and Gertrude's children's hospital both situated in Nairobi. RESULTS: Antimicrobial susceptibility data from a total of 731 non-duplicate S.aureus isolates was reviewed. Majority (79.2%) of the isolates were from pus swabs. Only 24 isolates were both cefoxitin and oxacillin resistant while 3 were resistant to oxacillin but susceptible to cefoxitin giving an overall MRSA prevalence of 3.7% (27/731). None of the isolates were resistant to mupirocin, linezolid, tigecycline, teicoplanin or vancomycin. CONCLUSION: The prevalence of MRSA in this study is much lower than what has been reported in most African countries. The significant change in antibiotic susceptibility compared to what has previously been reported in our hospital is most likely a consequence of the transition to an automated platform rather than a trend towards lower resistance rates.

The New Creatinine-Based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 Equation: Potential Impact on Screening for Chronic Kidney Disease in an Asymptomatic Black African Population.

BACKGROUND: In 2021, a new Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation was introduced that excluded race correction. We set out to compare estimated glomerular filtration rate (eGFR) determined using the creatinine-based CKD-EPI 2009 and 2021 equations and the reclassification of chronic kidney disease (CKD) eGFR staging to explore the potential ramifications of adopting the 2021 equation on reported eGFR and CKD staging. METHODS: We analyzed secondary data previously utilized to determine reference intervals among Black African individuals residing in urban towns in Kenya. Serum creatinine was measured using a standardized modified Jaffé kinetic method on a Beckman AU5800 analyzer. Glomerular filtration rate (GFR) was estimated using both the 2009 and 2021 CKD-EPI creatinine equations. Classification of CKD based on eGFR was performed using the Kidney Disease: Improving Global Outcomes (KDIGO) practice guidelines. RESULTS: Using 533 study samples, the median eGFR was highest when determined using the race-corrected CKD-EPI 2009 equation. The CKD-EPI 2021 equation yielded a median eGFR that was similar to the non-race-corrected CKD-EPI 2009 equation. The race-corrected CKD-EPI 2009 equation classified 93.6% of participants into CKD stage G1 compared with 85.6% by the CKD-EPI 2021 equation. The CKD-EPI 2021 equation classified 14.3% of participants into CKD stage G2 compared to 6.4% by the race-corrected CKD-EPI 2009 equation. CONCLUSIONS: The CKD-EPI 2021 equation gave a comparable eGFR to the non-race-corrected CKD-EPI 2009 equation and its implementation in laboratories reporting eGFR in Kenya will help in identifying patients with an appropriate decrease in renal function.

Post-vaccination SARS-CoV-2 IgG spike antibody responses among clinical and non-clinical healthcare workers at a tertiary facility in Kenya.

INTRODUCTION: Following the coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, vaccination became the main strategy against disease severity and even death. Healthcare workers were considered high-risk for infection and, thus, were prioritised for vaccination. METHODS: A follow-up to a SARS-CoV-2 seroprevalence study among clinical and non-clinical HCWs at the Aga Khan University Hospital, Nairobi, we assessed how vaccination influenced SARS-CoV-2 anti-spike IgG antibody responses and kinetics. Blood samples were drawn at two points spanning 6 to 18 months post-vaccination, and SARS-CoV-2 spike antibody levels were determined by enzyme-linked immunosorbent assay. RESULTS: Almost all participants, 98% (961/981), received a second vaccine dose, and only 8.5% (83/981) received a third dose. SARS-CoV-2 spike IgG antibodies were detected in 100% (961/961) and 92.7% (707/762) of participants who received two vaccine doses, with the first and second post-vaccine test, respectively, and in 100% (83/83) and 91.4% (64/70) of those who received three vaccine doses at the first and second post-vaccine test, respectively. Seventy-six participants developed mild infections, not requiring hospitalisation even after receiving primary vaccination. Receiving three vaccine doses influenced the anti-spike S/Co at both the first (p<0.001) and second post-vaccination testing (p<0.001). Of those who tested SARS-CoV-2 positive, the anti-spike S/Co ratio was significantly higher than those who were seronegative at the first post-vaccine test (p = 0.001). Side effects were reported by almost half of those who received the first dose, 47.3% (464/981), 28.9% (278/961) and 25.3% (21/83) of those who received the second and third vaccine doses, respectively. DISCUSSION AND CONCLUSION: Following the second dose of primary vaccination, all participants had detectable anti-spike antibodies. The observed mild breakthrough infections may have been due to emerging SARS-CoV-2 variants. Findings suggest that although protective antibodies are induced, vaccination protected against COVID-19 disease severity and not necessarily infection.

Corrigendum: Microbiota dynamics, metabolic and immune interactions in the cervicovaginal environment and their role in spontaneous preterm birth.

[This corrects the article DOI: 10.3389/fimmu.2023.1306473.].

The diagnostic accuracy of an initial point-of-care lactate at the emergency department as a predictor of in-hospital mortality among adult patients with sepsis and septic shock.

Background: In patients with sepsis, elevated lactate has been shown to be a strong predictor of in-hospital mortality. However, the optimal cutoff for rapidly stratifying patients presenting to the emergency department at risk for increased in-hospital mortality has not been well defined. This study aimed to establish the optimal point-of-care (POC) lactate cutoff that best predicted in-hospital mortality in adult patients presenting to the emergency department. Methods: This was a retrospective study. All adult patients who presented to the emergency department at the Aga Khan University Hospital, Nairobi, between 1 January 2018 and 31 August 2020 with suspected sepsis or septic shock and were admitted to the hospital were included in the study. Initial POC lactate results (GEM 3500® blood gas analyzer) and demographic and outcome data were collected. A receiver operating characteristic (ROC) curve for initial POC lactate values was plotted to determine the area under the curve (AUC). An optimal initial lactate cutoff was then determined using the Youden Index. Kaplan-Meier curves were used to determine the hazard ratio (HR) for the identified lactate cutoff. Results: A total of 123 patients were included in the study. They had a median age of 61 years [interquartile range (IQR) 41.0-77.0]. Initial lactate independently predicted in-hospital mortality [adjusted odds ratio (OR) 1.41 95% confidence interval (CI 1.06, 1.87) p = 0.018]. Initial lactate was found to have an area under the curve (AUC) of 0.752 (95% CI, 0.643 to 0.86). Additionally, a cutoff of 3.5 mmol/L was found to best predict in-hospital mortality (sensitivity 66.7%, specificity 71.4%, PPV 70%, NPV 68.2%). Mortality was 42.1% (16/38) in patients with an initial lactate of ≥ 3.5 mmol/L and 12.7% (8/63) in patients with an initial lactate of <3.5 mmol/L (HR, 3.388; 95% CI, 1.432-8.018; p < 0.005). Discussion: An initial POC lactate of ≥ 3.5 mmol/L best predicted in-hospital mortality in patients presenting with suspected sepsis and septic shock to the emergency department. A review of the sepsis and septic shock protocols will help in the early identification and management of these patients to reduce their in-hospital mortality.

Microbiota dynamics, metabolic and immune interactions in the cervicovaginal environment and their role in spontaneous preterm birth.

Differences in the cervicovaginal microbiota are associated with spontaneous preterm birth (sPTB), a significant cause of infant morbidity and mortality. Although establishing a direct causal link between cervicovaginal microbiota and sPTB remains challenging, recent advancements in sequencing technologies have facilitated the identification of microbial markers potentially linked to sPTB. Despite variations in findings, a recurring observation suggests that sPTB is associated with a more diverse and less stable vaginal microbiota across pregnancy trimesters. It is hypothesized that sPTB risk is likely to be modified via an intricate host-microbe interactions rather than due to the presence of a single microbial taxon or broad community state. Nonetheless, lactobacilli dominance is generally associated with term outcomes and contributes to a healthy vaginal environment through the production of lactic acid/maintenance of a low pH that excludes other pathogenic microorganisms. Additionally, the innate immunity of the host and metabolic interactions between cervicovaginal microbiota, such as the production of bacteriocins and the use of proteolytic enzymes, exerts a profound influence on microbial populations, activities, and host immune responses. These interplays collectively impact pregnancy outcomes. This review aims to summarize the complexity of cervicovaginal environment and microbiota dynamics, and associations with bacterial vaginosis and sPTB. There is also consideration on how probiotics may mitigate the risk of sPTB and bacterial vaginosis.

SARS-CoV-2 seroprevalence in pregnant women in Kilifi, Kenya from March 2020 to March 2022.

Background: Seroprevalence studies are an alternative approach to estimating the extent of transmission of SARS-CoV-2 and the evolution of the pandemic in different geographical settings. We aimed to determine the SARS-CoV-2 seroprevalence from March 2020 to March 2022 in a rural and urban setting in Kilifi County, Kenya. Methods: We obtained representative random samples of stored serum from a pregnancy cohort study for the period March 2020 to March 2022 and tested for antibodies against the spike protein using a qualitative SARS-CoV-2 ELISA kit (Wantai, total antibodies). All positive samples were retested for anti-SARS-CoV-2 anti-nucleocapsid antibodies (Euroimmun, ELISA kits, NCP, qualitative, IgG) and anti-spike protein antibodies (Euroimmun, ELISA kits, QuantiVac; quantitative, IgG). Results: A total of 2,495 (of 4,703 available) samples were tested. There was an overall trend of increasing seropositivity from a low of 0% [95% CI 0-0.06] in March 2020 to a high of 89.4% [95% CI 83.36-93.82] in Feb 2022. Of the Wantai test-positive samples, 59.7% [95% CI 57.06-62.34] tested positive by the Euroimmun anti-SARS-CoV-2 NCP test and 37.4% [95% CI 34.83-40.04] tested positive by the Euroimmun anti-SARS-CoV-2 QuantiVac test. No differences were observed between the urban and rural hospital but villages adjacent to the major highway traversing the study area had a higher seroprevalence. Conclusion: Anti-SARS-CoV-2 seroprevalence rose rapidly, with most of the population exposed to SARS-CoV-2 within 23 months of the first cases. The high cumulative seroprevalence suggests greater population exposure to SARS-CoV-2 than that reported from surveillance data.

Ferritin and its association with anaemia in a healthy adult population in Kenya.

BACKGROUND: Iron deficiency is the commonest cause of anaemia worldwide. Serum ferritin is the most sensitive non-invasive indicator of iron stores but its utility is compromised in inflammatory states as it is an acute phase reactant. This study sought to estimate the burden of iron deficiency in a healthy adult population residing in Kenya and to determine the association between various ferritin cut-offs and anaemia in a population known to have chronic low-grade inflammation. METHODS: Healthy adults aged 18-65 years were recruited from urban towns in 4 counties in Kenya at average altitudes of 1683-2099m above sea level as part of a global study conducted by the International Federation of Clinical Chemistry (IFCC) to determine reference intervals (RIs) for common laboratory tests. We analyzed complete blood count (CBC), C-reactive protein, iron, transferrin, transferrin saturation and ferritin data. RESULTS: We obtained data from 528 participants. There were 254 (48.1%) males and 274 females (51.9%). Based on a ferritin cut-off of 15 µg/L and Hb cut-offs of 14.5 g/dL and 12 g/dL, the prevalence of iron deficiency anaemia was 0.8% and 7.3% in males and females respectively. The odds of having anaemia was highest if one had a ferritin value less than 15 µg/L with a sensitivity of 28.6% and specificity of 98.4% in males, and sensitivity of 83.3% and specificity of 78.0% in females. CONCLUSION: Only the ferritin cut-off of 15 ug/L had an association with anaemia where it can be used for ruling out iron deficiency as the cause. Sex specific ferritin cut-offs for diagnosing iron deficiency in adults in sub-Saharan Africa need to be derived by comparing ferritin levels to stainable iron in bone marrow aspirates and trephines in order to ensure that we are using appropriate clinical decision limits.